Combination treatments comprising c-met antagonists and b-raf antagonists

Abstract

The present invention relates generally to the fields of molecular biology and growth factor regulation. More specifically, the invention relates to therapies for the treatment of pathological conditions, such as cancer.

1 : A method for treating a patient with cancer comprising administering to the patient an effective amount of B-raf antagonist and c-met antagonist. 
     
     
         2 : The method of  claim 1 , wherein the patient has an increased likelihood of developing resistance to B-raf antagonist. 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 : The method of  claim 1 , wherein the cancer is a B-raf antagonist resistant cancer. 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 : The method of  claim 1 , wherein the patient's cancer has been shown to express B-raf biomarker. 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 : The method of  claim 8 , wherein mutant B-raf biomarker expression in the patient's cancer is determined using a method comprising (a) performing one or more of gene expression profiling, PCR hybridization assay, in situ hybridization, 5′ nuclease assay mutation detection assay, RNA-seq, microarray analysis, SAGE, MassARRAY technique, or FISH on a sample and (b) determining expression of mutant B-raf biomarker in the sample. 
     
     
         12 : The method of  claim 11 , wherein mutant B-raf biomarker expression in the patient's cancer is determined using a method comprising (a) performing PCR on genomic DNA extracted from a patient cancer sample and (b) determining expression of mutant B-raf biomarker in the sample. 
     
     
         13 : The method of  claim 1 , wherein the patient's cancer has been shown to express c-met biomarker. 
     
     
         14 : The method of  claim 13 , wherein c-met biomarker is a polypeptide. 
     
     
         15 : The method of  claim 14 , wherein c-met biomarker expression is determined using immunohistochemistry (IHC). 
     
     
         16 : The method of  claim 15 , wherein c-met biomarker expression is determined by determining expression of hepatocyte growth factor (HGF). 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 : The method of  claim 1 , wherein the c-met antagonist is an antagonist anti-c-met antibody. 
     
     
         20 : The method of  claim 1 , wherein the c-met antagonist is one or more of onartuzumab, crizotinib, tivantinib, carbozantinib, MGCD-265, ficlatuzumab, humanized TAK-701, rilotumumab, foretinib, h224G11, DN-30, MK-2461, E7050, MK-8033, PF-4217903, AMG208, JNJ-38877605, EMD1204831, INC-280, LY-2801653, SGX-126, RP1040, LY2801653, BAY-853474, and/or LA480. 
     
     
         21 : The method of  claim 1 , wherein the B-raf antagonist is one or more of sorafenib, PLX4720, PLX-3603, GSK2118436, GDC-0879, N-(3-(5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide, vemurafenib, GSK 2118436, RAF265 (Novartis), XL281, ARQ736, BAY73-4506. 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 : The method of  claim 1 , wherein the B-raf antagonist and the c-met antagonist are administered simultaneously. 
     
     
         25 : The method of  claim 1 , wherein the B-raf antagonist and the c-met antagonist are administered sequentially. 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 : The method of  claim 1 , further comprising administering at least one additional treatment to said subject. 
     
     
         29 : The method of  claim 1 , wherein the cancer is melanoma, colorectal, ovarian, breast or papillary thyroid. 
     
     
         30 . (canceled) 
     
     
         31 : The method of  claim 1 , wherein the cancer is resistant to B-raf antagonist. 
     
     
         32 : The method of  claim 1 , wherein the patient has not been previously treated with B-raf antagonist. 
     
     
         33 . (canceled) 
     
     
         34 : A method for identifying a patient having cancer as a candidate for treatment with a B-raf antagonist and a c-met antagonist, comprising (a) determining that the patient's cancer expresses c-met biomarker; and (b) identifying the patient as a candidate for treatment with a B-raf antagonist and a c-met antagonist. 
     
     
         35 : A method for identifying a patient having cancer as at risk of developing resistance to a B-raf antagonist, comprising (a) determining that the patient's cancer expresses c-met biomarker; and (b) identifying the patient as at risk of developing resistance to a B-raf antagonist 
     
     
         36 : The method of  claim 34 , wherein subsequent to steps (a) and (b), the patient is treated with an effective amount of a c-met antagonist and a B-raf antagonist. 
     
     
         37 : A method of determining therapeutic efficacy of a B-raf antagonist for treating cancer in a patient comprising determining the presence of c-met biomarker and/or B-raf biomarker in a sample obtained from said patient by immunoassay, elisa, hybridization assay, PCR, 5′ nuclease assay, IHC, and/or RT-PCR, and selecting the patient for treatment with a B-raf antagonist. 
     
     
         38 : The method of  claim 37 , further comprising selecting the patient for treatment with a c-met antagonist. 
     
     
         39 : The method of  claim 38 , further comprising treating the patient with an effective amount of B-raf antagonist and c-met antagonist. 
     
     
         40 . (canceled) 
     
     
         41 : A kit comprising a c-met antagonist and a B-raf antagonist. 
     
     
         42 : The kit of  claim 41 , further comprising instructions for a method for treating a melanoma patient comprising administering an effective amount of a c-met antagonist and B-raf antagonist to the patient. 
     
     
         43 . (canceled)